vasoactive-intestinal-peptide and Epilepsy--Temporal-Lobe

In mesial temporal lobe epilepsy (MTLE), seizures typically arise in the hippocampus or other mesial temporal lobe structures. The aetiology of MTLE epileptogenesis in still unknown, yet putative precipitating events such as trauma, complex febrile seizures, status epilepticus, inflammatory insults, or ischemia have been implicated. MTLE is commonly associated to a high degree of hippocampal sclerosis (HS) leading to frequent anti-epileptic drug refractoriness. Thus, the aim of recent therapeutic strategies has shifted from control of symptomatic seizures to putative prevention of epileptogenic processes. Vasoactive intestinal peptide (VIP) acts as a neurotransmitter, neurotrophic or neuroprotective factor in the central nervous system (CNS), also displaying anti-inflammatory and neurogenic actions. In the hippocampus, a brain area implicated in learning and memory, VIP released from basket cells and/or interneuron-selective interneurons controls GABAergic transmission and pyramidal cell activity influencing hippocampal-dependent synaptic plasticity (long-term potentiation and long-term depression) and cognition. VPAC

Topics: Animals; Epilepsy, Temporal Lobe; Hippocampus; Humans; Neuronal Plasticity; Neuroprotection; Receptors, Neuropeptide; Sclerosis; Synaptic Transmission; Vasoactive Intestinal Peptide

The subiculum, a key output region of the hippocampus, is increasingly recognized as playing a crucial role in seizure initiation and spread. The subiculum consists of glutamatergic pyramidal cells, which show alterations in intrinsic excitability in the course of epilepsy, and multiple types of GABAergic interneurons, which exhibit varying characteristics in epilepsy. In this study, we aimed to assess the role of the vasoactive intestinal peptide interneurons (VIP-INs) of the ventral subiculum in the pathophysiology of temporal lobe epilepsy. We observed that an anatomically restricted inhibition of VIP-INs of the ventral subiculum was sufficient to reduce seizures in the intrahippocampal kainic acid model of epilepsy, changing the circadian rhythm of seizures, emphasizing the critical role of this small cell population in modulating TLE. As we expected, permanent unilateral or bilateral silencing of VIP-INs of the ventral subiculum in non-epileptic animals did not induce seizures or epileptiform activity. Interestingly, transient activation of VIP-INs of the ventral subiculum was enough to increase the frequency of seizures in the acute seizure model. Our results offer new perspectives on the crucial involvement of VIP-INs of the ventral subiculum in the pathophysiology of TLE. Given the observed predominant disinhibitory role of the VIP-INs input in subicular microcircuits, modifications of this input could be considered in the development of therapeutic strategies to improve seizure control.

Topics: Animals; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Interneurons; Kainic Acid; Seizures; Vasoactive Intestinal Peptide

Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls.. This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay.. The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05).. The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Topics: Cross-Sectional Studies; Drug Resistance; Epilepsy, Temporal Lobe; Fibronectins; Ghrelin; Humans; Nucleobindins; Vasoactive Intestinal Peptide

The distribution of the VIP receptor in the human hippocampus was studied by receptor autoradiography using [3-iodotyrosyl-125I]Vasoactive Intestinal Peptide (VIP) as a ligand, and the relationship of receptor distribution to the distribution of the peptide (visualized by immunocytochemistry) was examined in hippocampi surgically removed from patients with medically intractable temporal lobe epilepsy (TLE) and hippocampi obtained at autopsy from neurologically normal subjects. In the autopsy hippocampi and hippocampi from TLE patients with extrahippocampal temporal lobe lesions [125I]VIP binding was highest in the dentate molecular layer, with lower levels in the fields of Ammon's Horn (CA fields) and the subiculum. In hippocampi from patients with no temporal lobe lesions but considerable hippocampal neuronal loss there were significant elevations in the levels of ligand binding in all CA fields and the subiculum. Ligand binding densities in all CA fields of the patient hippocampi were strongly negatively correlated with neuronal numbers. Immunocytochemical localization of VIP shows no obvious change in the distribution patters of VIP immunoreactivity in the patient groups. This is the first demonstration of VIP and its receptor distribution in the human hippocampus. It is suggested that the elevated levels of receptor binding in the hippocampal seizure focus may indicate a mechanism for greater excitability of neurons and/or for their survivability in the face of the increased excitation and potential for injury in a seizure focus.

Topics: Adolescent; Adult; Cell Count; Child; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Immunohistochemistry; Male; Middle Aged; Neuroglia; Neurons; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide